Regulator of G-protein signaling (RGS)-2 is a potent inhibitor of Gαq vasoconstrictor signaling which mediates the renal and cardiovascular actions of several vasoconstrictor agonists, including noradrenaline, angiotensin II, vasopressin, and endothelin-1, which is highly integrated within the nitric oxide (NO)-mediated vasodilatory pathway.Citation1 Disruption of the RGS-2 gene, in fact, prolongs vasoconstrictor responses of the peripheral resistance vasculature in vivo and of aortic vascular smooth muscle cells in vitro.Citation2 RGS-2 was also shown to regulate vasopressin responses in cortical collecting duct in vivo, negatively regulating V2 type of vasopressin receptor signaling in the kidney.Citation3 We have recently demonstrated in humans that RGS-2 plays an important role in renin–angiotensin system (RAS) regulation, both in hypertension,Citation4 where its level is reduced, and in conditions characterized by potassium, sodium, and volume depletion and normo/hypotension such as Bartter's/Gitelman's syndrome, where its level is maximally increased.Citation5 Taken together these findings suggest that the control of RGS-2 protein level and function appears to be extremely important for the regulation of both vascular resistance and blood volume.
The kidney responds to changes in renal perfusion pressure via autoregulation. When the blood pressure falls, in fact, the dilation of preglomerular arterioles, mediated by vasodilating prostaglandin and NO, and the concomitant vasoconstriction of the postglomerular arterioles, mainly under the influence of angiotensin II, maintains a constant glomerular capillary hydrostatic pressure.
An imbalance between these pathways, in association with direct tubular obstruction and injury, may play a central role in acute kidney injury (AKI)-complicating rhabdomyolysis.
The epidemiology, pathogenesis, and treatment of the myoglobinuria-induced AKI have been recently reviewed.Citation6 A correlation between creatine kinase (CK) and AKI and increased risk of AKI according to a scoring system including CK, potassium, lactate dehydrogenase, and uric acid levels has been described.Citation6,Citation7
A 28-year-old man was referred to our nephrology service for exertional rhabdomyolysis with mild AKI (peaked serum creatinine at 199 μmol/L). He was immediately treated with intravenous fluids repletion and electrolyte replacement and monitored with bioelectrical impedance vector analysis. He underwent a favorable and rapid outcome despite a CK level of 161,000 UI/L and an adverse scoring system, recovering normal capacity in urine acidification and concentration at follow-up.
Our patient had been previously randomly recruited as a healthy normotensive control, without diabetes, cardiac failure, evidence for coronary heart disease, or renal failure in a study of our group performed to evaluate RGS-2 protein level in hypertensive patientsCitation4 and was found with a high-normal RGS-2 protein level. In consideration of the pathogenesis of myoglobinuria-induced AKI and RGS-2 actions, a low protein level of RGS-2 could instead impair the prompt response to volume repletion-based treatment, which remains the main clinical management of rhabdomyolysis. A study of RGS-2 expression influence on the outcome of rhabdomyolysis-induced AKI could be useful to give further insights.
Giacomo Strapazzon
Department of Clinical and Experimental Medicine,
Clinica Medica 4, University of Padova,
Via Giustiniani 2, Padova 35128, Italy
Antonio Piccoli
Department of Nephrology, University of Padova,
Via Giustiniani 2, Padova 35128, Italy
Lorenzo A. Calò
Department of Clinical and Experimental Medicine,
Clinica Medica 4, University of Padova,
Via Giustiniani 2, Padova 35128, Italy
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